Abstract
Uncertainty in computed tomography (CT)-based range prediction substantially impairs the accuracy of proton therapy. Direct determination of the stopping-power ratio (SPR) from dual-energy CT (DECT) has been proposed (DirectSPR), and initial validation studies in phantoms and biological tissues have proven a high accuracy. However, a thorough validation of range prediction in patients has not yet been achieved by any means. Here, we present the first systematic validation of CT-based proton range prediction in patients using prompt gamma imaging (PGI). A PGI slit camera system with improved positioning accuracy, using a floor-based docking station, was used. Its overall uncertainty for range prediction validation was determined experimentally with both x-ray and beam measurements. The accuracy of range prediction in patients was determined from clinical PGI measurements during hypofractionated treatment of 5 patients with prostate cancer - in total 30 fractions with in-room control-CTs. For each pencil-beam-scanning spot, the range shift was obtained by comparing the PGI measurement to a control-CT-based PGI simulation. Three different SPR prediction approaches were applied in simulations: a standard CT-number-to-SPR conversion (Hounsfield look-up table [HLUT]), an adapted HLUT (DECT optimized), andDirectSPR. The spot-wise weighted mean range shift from all spots served as a measure for the accuracy of the respective range prediction approach. A mean range prediction accuracy of 0.0% ± 0.5%, 0.3% ± 0.4%, and 1.8% ± 0.4% was obtained for DirectSPR, adapted HLUT, and standard HLUT, respectively. The overall validation uncertainty of the second-generation PGI slit camera is about 1mm (2σ) for all approaches, which is smaller than the range prediction uncertainty for deep-seated tumors. For the first time, range prediction accuracy was assessed in clinical routine using PGI range verification in prostate cancer treatments. Both DECT-derived range prediction approaches agree well with the measured proton range from PGI verification, whereas the standard HLUT approach differs relevantly. These results endorse the recent reduction of clinical safety margins in DirectSPR-based treatment planning in our institution.
Highlights
The benefit of sparing healthy tissue in proton therapy (PT) strongly relies on precise and accurate prediction of the proton range during treatment planning, which is based on xray computed tomography (CT) scans.[1,2] The nominal uncertainty of range prediction from the conversion of CT numbers (CTN) to the tissue-specific stopping-power ratio (SPR) used for treatment planning—using a generic Hounsfield look-up table (HLUT)3—substantially limits the overall accuracy in PT.[4,5] safety margins of 2.5% to 3.5% of the proton range plus 1 to 3 mm are commonly considered in treatment planning, corresponding to about 10 mm for deep-seated tumor sites such as the prostate.[6]
Second-generation prompt gamma imaging (PGI) slit camera The basic principle of the PGI slit camera relies on the projection of the emission profile of prompt gamma (PG) radiation along the proton path onto a spatially resolved detector through a tungsten knife-edge slit collimator (Fig. 1).[19]
After careful consideration with our medical physicists and radiation therapy technicians (RTTs), including review of the control CT scan (cCT)-planning CT scan (pCT) registrations, a standard uncertainty of 0.82 mm (2s) in beam direction was estimated for the rigid CT registration (II), assuming a triangular uncertainty distribution with width §1 mm.[22]
Summary
The benefit of sparing healthy tissue in proton therapy (PT) strongly relies on precise and accurate prediction of the proton range during treatment planning, which is based on xray computed tomography (CT) scans.[1,2] The nominal uncertainty of range prediction from the conversion of CT numbers (CTN) to the tissue-specific stopping-power ratio (SPR) used for treatment planning—using a generic Hounsfield look-up table (HLUT)3—substantially limits the overall accuracy in PT.[4,5] safety margins of 2.5% to 3.5% of the proton range plus 1 to 3 mm are commonly considered in treatment planning, corresponding to about 10 mm for deep-seated tumor sites such as the prostate.[6]. The recent clinical introduction of range prediction from dual-energy CT (DECT), enabling a direct patient-specific voxel-wise SPR calculation (DirectSPR),[40] was an important milestone for improving the accuracy of CT-based range prediction by considering patient- and tissue-specific variabilities in CTN-to-SPR conversion.[7] The superior accuracy of the DirectSPR approach has been validated in experiments with homogeneous tissue surrogates,[8] samples of biological tissue,[9,10,11,12] and a heterogeneous anthropomorphic phantom.[13] neither DirectSPR nor HLUT approaches for range prediction have so far been systematically validated in patients themselves. The recent introduction of reduced safety margins of 1.7% + 2 mm for brain tumors and 2.0% + 2 mm for prostate tumors in DirectSPRbased treatment planning at the PT facility in Dresden (Germany)[40] highlights the relevance of such validation for patient treatments at our institute and beyond. A comprehensive uncertainty evaluation was performed based on phantom and tissue validation,[40] an independent validation in patients would support the change in clinical treatment planning and foster the clinical implementation of DECT-based planning at other institutions
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